A team of U of T researchers has measured the effects on younger middle-aged women’s cognitive and brain health of a surgical procedure known as bilateral salpingo-oophorectomies (BSO), the removal of both ovaries and fallopian tubes.
They found that BSOs put women at risk of worsening neuropsychological performance, even in early midlife, potentially presaging the already well documented two-fold increase in the risk of late-life Alzheimer’s disease (AD) in this population.
In this population, BSOs were performed as a prevention against breast and ovarian cancer in women with a genetic predisposition for breast cancer. They are often performed 10 to 15 years before the onset of spontaneous menopause.
“BSOs lead to the loss of a key estrogen, 17-b-estradiol, which is one factor we have found to be associated with increased risk of subjective cognitive decline (SCD),” says Noelia Calvo, a postdoctoral researcher in the Faculty of Arts & Science’s Department of Psychology and first author of a paper describing the study.
“And SCD — cognitive decline that hasn’t shown up in clinical tests but is indicated by a patient’s self-reported memory problems — is a strong predictor of late-life AD,” she says.
The study was conducted with the participation of 333 Canadian women with and without BSOs, some of whom reported SCD. The women who had BSOs had the procedure before they were 49 years old. In the study, cognitive health was determined by measuring verbal memory, verbal learning and spatial working memory. Magnetic resonance imaging measured grey matter volumes.
The researchers also determined that BSOs lead to a decrease in the volume of grey matter in these women's brains, particularly in regions sensitive to estradiol and in regions important for mood, memory and language.
“The effect of this procedure on brain health in early midlife women is very understudied as these kinds of changes are primarily expected much later in women’s lives,” says Gillian Einstein, principal investigator on the study.
Einstein is a professor of cognitive neuroscience in the Department of Psychology and the Wilfred and Joyce Posluns Chair in Women’s Brain Health and Aging; she is cross-appointed to the Dalla Lana School of Public Health at the University of Toronto and Baycrest’s Rotman Research Institute.
As the researchers point out, there is much focus in later-midlife menopause — known as spontaneous menopause (SM) — as an inflection point in a woman’s cognitive health.
But even in early-midlife, BSOs may have a greater effect on women’s cognitive and brain health than later-life SM. In addition, the researchers explain that a better understanding of the effects of BSOs in early midlife may be an important window into some of the earliest changes in women leading to late-life dementia.
“What we're doing is studying the effects of BSOs on younger middle-aged women because it's important to understand the earliest cognitive and brain changes in order to intervene at the earliest times possible,” says Einstein.
The team’s findings are described in the paper, ‘Cognitive and brain health in women with early bilateral salpingo-oophorectomy: Implications for risk, resilience and subjective cognitive decline’, published in Alzheimer’s and Demetia, the journal of the Alzheimer’s Association.
In addition to Calvo and Einstein, the paper’s University of Toronto co-authors include researchers from the Department of Psychology and the Faculty of Medicine.
The findings suggest early midlife strategies for mitigating cognitive decline. For example, because BSOs lead to a loss of estradiol, the research underlines the potential of estradiol therapy in reducing the cognitive and brain effects of the surgery.
The study also underscores the importance of language processing in general — reading, writing, learning and speaking multiple languages — as a resilience factor.
According to Calvo, “The verbal IQ finding is important because some of the most common memory complaints reported in our cohort are related to remembering specific words—for example, names of people, movies, books.
“And we found decreases in gray matter volume in areas important for speech production and language processing, for example, in the region known as Broca’s area. Thus, the fact that verbal IQ is associated with less odds of SCD indicates that verbal skills could play a key role in mitigating cognitive risks in this population.”
Einstein adds, “We tend to think of Alzheimer's disease the way we think of other diseases. We think you get hit with it and then you have it.
“But instead, it's probably something that's been happening to you for a long time before it's diagnosed. So, anything that you do that’s good for your brain in early in life may counteract the early life changes that might lead to the late life brain changes diagnosed as Alzheimer's.”
Approximately 750,000 Canadians live with Alzheimer's disease or another form of dementia, with AD the ninth leading cause of all deaths in Canada in 2022.
“And three quarters of Canadians with Alzheimer's disease are women,” says Einstein. “So, in order to understand and find treatments for the majority of people with AD, we need to understand how it progresses in women.
“Until recently, researchers have not been doing that. We’re trying to correct that.”
More Information
To learn more about this study or to speak to its authors, please contact:
- Michael Pereira
Communications Officer, Department of Psychology, University of Toronto
psy.communications.officer@utoronto.ca
Funding
This work was supported by the following bodies:
- Wilfred and Joyce Posluns Chair in Women’s Brain Health and Aging from the Posluns Family Foundation
- Canadian Institutes of Health Research (CIHR)
- Ontario Brain Institute and The Centre for Aging + Brain Health Innovation (CABHI)
- Canadian Cancer Society
- Canadian Consortium on Neurodegeneration in Aging (CCNA)
- Jacqueline Ford Gender and Health Fund